Role of nanoscale antigen organization on B-cell activation probed using DNA origami.
Journal
Nature nanotechnology
ISSN: 1748-3395
Titre abrégé: Nat Nanotechnol
Pays: England
ID NLM: 101283273
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
12
06
2019
accepted:
27
05
2020
pubmed:
1
7
2020
medline:
22
12
2020
entrez:
1
7
2020
Statut:
ppublish
Résumé
Vaccine efficacy can be increased by arraying immunogens in multivalent form on virus-like nanoparticles to enhance B-cell activation. However, the effects of antigen copy number, spacing and affinity, as well as the dimensionality and rigidity of scaffold presentation on B-cell activation remain poorly understood. Here, we display the clinical vaccine immunogen eOD-GT8, an engineered outer domain of the HIV-1 glycoprotein-120, on DNA origami nanoparticles to systematically interrogate the impact of these nanoscale parameters on B-cell activation in vitro. We find that B-cell signalling is maximized by as few as five antigens maximally spaced on the surface of a 40-nm viral-like nanoparticle. Increasing antigen spacing up to ~25-30 nm monotonically increases B-cell receptor activation. Moreover, scaffold rigidity is essential for robust B-cell triggering. These results reveal molecular vaccine design principles that may be used to drive functional B-cell responses.
Identifiants
pubmed: 32601450
doi: 10.1038/s41565-020-0719-0
pii: 10.1038/s41565-020-0719-0
pmc: PMC7415668
mid: NIHMS1598014
doi:
Substances chimiques
AIDS Vaccines
0
Antigens, Viral
0
HIV Envelope Protein gp120
0
gp120 protein, Human immunodeficiency virus 1
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
716-723Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : NIBIB NIH HHS
ID : R21 EB026008
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI048240
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI146581
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143740
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH112694
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
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